The biological control of oxygen transport by erythrocytes is disturbed in a number of disease processes such as the thalassemias, sickle-cell disease, and other hemoglobinopahies. These diseases have in common alterations in protein structure which produce altered cooperativity, instability, or both, and lead to a variety of spectroscopy to measure molecular changes in hemoglobin conformation with ligand binding or other modifications that lead to diseased states. We focus on single vibrating groups in the protein such as individual cysteine SH groups, and in the heme or coordinated ligand. Definition of structural interactions at these points allows development of a pattern of movements for the entire protein which constitutes biological control. For example, movements at the heme with ligation lead to small shifts (much less than 0.1A) in H-bonded SH...0 distance of alpha-104 cysteine residues measured by infrared frequency shifts that range from 4/cm to 0.1/cm. Structural interactions at other locations also lead to change in absorption band intensity or half-band width. No spectroscopic method other than FTIR as specially adapted in our laboratory has the combination of sensitivity and photometric and frequency accuracy that is required for these vibrational measurements in biological materials. Studies of both diseased and normal states will lead to a detailed understanding of the molecular basis for biological control of oxygen transport in hemoglobin and serve as a model for other systems.